Gene Symbol: ZSCAN4
Description: zinc finger and SCAN domain containing 4
Alias: ZNF494, zinc finger and SCAN domain-containing protein 4, zinc finger protein 494
Species: human
Products:     ZSCAN4

Top Publications

  1. Nishihara K, Shiga T, Nakamura E, Akiyama T, Sasaki T, Suzuki S, et al. Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression. Stem Cell Reports. 2019;12:305-318 pubmed publisher
    ..Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an ..
  2. Park H, Hwang I, Choi K, Jeong H, Lee J, Hong S. Generation of induced pluripotent stem cells without genetic defects by small molecules. Biomaterials. 2015;39:47-58 pubmed publisher
    ..molecules preserved the genomic stability of iPSCs by inhibiting DNA double-strand breaks (DSBs) and activating Zscan4 gene...
  3. Mitsuhashi H, Ishimaru S, Homma S, Yu B, Honma Y, Beermann M, et al. Functional domains of the FSHD-associated DUX4 protein. Biol Open. 2018;7: pubmed publisher
    ..construct to DUX4-FL for (i) activation of a DUX4 promoter reporter, (ii) expression of the DUX4-FL target gene ZSCAN4, (iii) effect on cell viability, (iv) activation of endogenous caspases, and (v) level of protein ..
  4. Fu H, Tian C, Ye X, Sheng X, Wang H, Liu Y, et al. Dynamics of Telomere Rejuvenation during Chemical Induction to Pluripotent Stem Cells. Stem Cell Reports. 2018;11:70-87 pubmed publisher
    ..We find that histone crotonylation induced by crotonic acid can activate two-cell genes, including Zscan4; maintain telomeres; and promote CiPSC generation...
  5. Zhang B, Fu D, Xu Q, Cong X, Wu C, Zhong X, et al. The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1. Nat Commun. 2018;9:1723 pubmed publisher
    ..Here we report that the transcription factor Zscan4 is elevated for expression by an ATM-TRAF6-TAK1 axis during the acute DNA damage response and enables a long term ..
  6. Amano T, Hirata T, Falco G, Monti M, Sharova L, Amano M, et al. Zscan4 restores the developmental potency of embryonic stem cells. Nat Commun. 2013;4:1966 pubmed publisher
    ..Previously, we have shown that ES cells oscillate between Zscan4(-) and Zscan4(+) states, and the transient activation of Zscan4 is required for the maintenance of telomeres and ..
  7. Guo R, Ye X, Yang J, Zhou Z, Tian C, Wang H, et al. Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells. Nat Commun. 2018;9:2620 pubmed publisher
    ..Notably, feeders facilitate heterogeneous transcription of 2-cell genes including Zscan4 and telomere elongation. Moreover, feeders produce Fstl1 that together with BMP4 periodically activate Zscan4...
  8. Cruz J, Hupper N, Wilson L, Concannon J, Wang Y, Oberhauser B, et al. Protein kinase A activation inhibits DUX4 gene expression in myotubes from patients with facioscapulohumeral muscular dystrophy. J Biol Chem. 2018;293:11837-11849 pubmed publisher
    ..in a phenotypic screen using FSHD patient-derived muscle cells, a zinc finger and SCAN domain-containing 4 (ZSCAN4)-based reporter gene assay for measuring DUX4 activity, and ∼3,000 small molecules...
  9. Costello I, Biondi C, Taylor J, Bikoff E, Robertson E. Smad4-dependent pathways control basement membrane deposition and endodermal cell migration at early stages of mouse development. BMC Dev Biol. 2009;9:54 pubmed publisher
    ..We also observed an increase in non-canonical potency markers (Pramel7, Tbx3, Zscan4), germ cell markers (Aire, Tuba3a, Dnmt3l) as well as early endoderm markers (Dpp4, H19, Dcn)...

More Information


  1. Kwon Y, Paek J, Cho H, Lee C, Lee H, Park I, et al. Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC. Biomaterials. 2015;59:102-15 pubmed publisher
    ..By screening the genes differentially expressed between mouse iPS and mES cells, Zscan4, which is known to enhance telomere elongation and stabilize genomic DNA, was identified as a strong candidate to ..
  2. Amano T, Jeffries E, Amano M, Ko A, Yu H, Ko M. Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. DNA Res. 2015;22:331-42 pubmed publisher
    ..Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in ..
  3. Ko M. Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4. Curr Top Dev Biol. 2016;120:103-24 pubmed publisher
    ..In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation ..
  4. Jiang L, Chen H, Pinello L, Yuan G. GiniClust: detecting rare cell types from single-cell gene expression data with Gini index. Genome Biol. 2016;17:144 pubmed publisher
    ..of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and ..
  5. Rodriguez Terrones D, Gaume X, Ishiuchi T, Weiss A, Kopp A, Kruse K, et al. A molecular roadmap for the emergence of early-embryonic-like cells in culture. Nat Genet. 2018;50:106-119 pubmed publisher
    ..approach, we identified an intermediate population characterized by expression of the transcription factor ZSCAN4 as a precursor of 2-cell-like cells...
  6. Sharova L, Sharov A, Piao Y, Stagg C, Amano T, Qian Y, et al. Emergence of undifferentiated colonies from mouse embryonic stem cells undergoing differentiation by retinoic acid treatment. In Vitro Cell Dev Biol Anim. 2016;52:616-24 pubmed publisher
    ..cultured in the presence of a leukemia inhibitory factor (LIF) also result in the upregulation of a gene called Zscan4, whose transient expression is a marker for undifferentiated ESCs...
  7. Nakai Futatsugi Y, Niwa H. Zscan4 Is Activated after Telomere Shortening in Mouse Embryonic Stem Cells. Stem Cell Reports. 2016;6:483-495 pubmed publisher
    b>ZSCAN4 is a DNA-binding protein that functions for telomere elongation and genomic stability. In vivo, it is specifically expressed at the two-cell stage during mouse development...
  8. Choi S, Gearhart M, Cui Z, Bosnakovski D, Kim M, Schennum N, et al. DUX4 recruits p300/CBP through its C-terminus and induces global H3K27 acetylation changes. Nucleic Acids Res. 2016;44:5161-73 pubmed publisher
    ..Chromatin immunoprecipitation shows that DUX4 recruits p300 to its target gene, ZSCAN4, displaces histone H3 from the center of its binding site, and induces H3K27Ac in its vicinity, but C-terminal ..
  9. Zhang Q, Dan J, Wang H, Guo R, Mao J, Fu H, et al. Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells. Sci Rep. 2016;6:19852 pubmed publisher
    ..One of 2-cell genes, Zscan4, has been shown to be responsible for telomere maintenance, genomic stability and pluripotency of mouse ESCs...
  10. Akiyama T, Xin L, Oda M, Sharov A, Amano M, Piao Y, et al. Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells. DNA Res. 2015;22:307-18 pubmed publisher
    ..We previously showed that infrequent bursts of Zscan4 expression (Z4 events) are important for the maintenance of telomere length and genome stability in mESCs...
  11. Hendrickson P, Dorais J, Grow E, Whiddon J, Lim J, Wike C, et al. Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nat Genet. 2017;49:925-934 pubmed publisher
    ..retrogene, DUX4, encodes a transcription factor that activates hundreds of endogenous genes (for example, ZSCAN4, KDM4E and PRAMEF-family genes) and retroviral elements (MERVL/HERVL family) that define the cleavage-specific ..
  12. Yang J, Guo R, Wang H, Ye X, Zhou Z, Dan J, et al. Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs. Cell Rep. 2016;15:1809-21 pubmed publisher
    ..Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening...
  13. Eckersley Maslin M, Svensson V, Krueger C, Stubbs T, Giehr P, Krueger F, et al. MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs. Cell Rep. 2016;17:179-192 pubmed publisher
    ..cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos...
  14. Lee K, Gollahon L. ZSCAN4 and TRF1: A functionally indirect interaction in cancer cells independent of telomerase activity. Biochem Biophys Res Commun. 2015;466:644-9 pubmed publisher
    Recently, the newly identified embryonic stem cell marker, Zinc finger and SCAN domain containing 4 gene (ZSCAN4), which plays a key role in genomic stability by regulating telomere elongation, was shown to co-localize with TRF1 foci...
  15. Dan J, Liu Y, Liu N, Chiourea M, Okuka M, Wu T, et al. Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin silencing. Dev Cell. 2014;29:7-19 pubmed publisher
    ..that telomere-associated protein Rif1 is required to maintain telomere length homeostasis by negatively regulating Zscan4 expression, a critical factor for telomere elongation by recombination...
  16. Ishiguro K, Nakatake Y, Chikazawa Nohtomi N, Kimura H, Akiyama T, Oda M, et al. Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos. In Vitro Cell Dev Biol Anim. 2017;53:179-190 pubmed publisher
    Mouse Zinc finger and SCAN domain containing 4 (Zscan4) is encoded in multiple copies of Zscan4 genes, which are expressed in late two-cell stage preimplantation embryos and in 1-5% of the embryonic stem (ES) cell population at a given ..
  17. Ishiguro K, Monti M, Akiyama T, Kimura H, Chikazawa Nohtomi N, Sakota M, et al. Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis. In Vitro Cell Dev Biol Anim. 2017;53:167-178 pubmed publisher
    Mouse zinc finger and SCAN domain containing 4 (Zscan4) proteins, which are encoded by multiple copies of Zscan4 genes, are expressed specifically in preimplantation embryos in vivo and embryonic stem (ES) cells in vitro...
  18. Dan J, Rousseau P, Hardikar S, Veland N, Wong J, Autexier C, et al. Zscan4 Inhibits Maintenance DNA Methylation to Facilitate Telomere Elongation in Mouse Embryonic Stem Cells. Cell Rep. 2017;20:1936-1949 pubmed publisher
    ..b>Zscan4, which exhibits a burst of expression in 2C-like mESCs, is required for telomere extension in these cells...
  19. Portney B, Khatri R, Meltzer W, Mariano J, Zalzman M. ZSCAN4 is negatively regulated by the ubiquitin-proteasome system and the E3 ubiquitin ligase RNF20. Biochem Biophys Res Commun. 2018;498:72-78 pubmed publisher
    b>Zscan4 is an early embryonic gene cluster expressed in mouse embryonic stem and induced pluripotent stem cells where it plays critical roles in genomic stability, telomere maintenance, and pluripotency...
  20. Lee K, Gollahon L. Zscan4 interacts directly with human Rap1 in cancer cells regardless of telomerase status. Cancer Biol Ther. 2014;15:1094-105 pubmed publisher
    ..Recently, the newly identified embryonic stem cell marker, Zinc finger and SCAN domain-containing 4 gene (Zscan4), was shown to be a telomere-associated protein, co-localizing to the shelterin complex...
  21. Zalzman M, Falco G, Sharova L, Nishiyama A, Thomas M, Lee S, et al. Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature. 2010;464:858-63 pubmed publisher
    ..However, the genes contributing to this stability remain obscure. We previously identified Zscan4 as a specific marker for two-cell embryo and ES cells...